Biology subjects

Gouttenoire, J.

Publications and source records attributed to Gouttenoire, J..

2 recordsLinked to original sources

bioRxiv2023

Influence of amino acid substitutions in capsid proteins of coxsackievirus B5 on free chlorine and thermal inactivation

The sensitivity of enteroviruses to disinfectants varies among genetically similar variants and coincides with amino acid changes in capsid proteins, though the effect of individual substitutions remains unknown. Here, we employed reverse genetics to investigate how amino acid substitutions in coxsackievirus B5 (CVB5) capsid proteins affect its sensitivity to free chlorine and heat treatment. Of ten amino acid changes hypothesized to coincide with free chlorine resistance, none significantly reduced the chlorine-sensitivity, indicating a minor role of the capsid composition in chlorine sensitivity of CVB5. Conversely, we observed reduced heat sensitivity in mutants with substitutions at the C-terminal region of the viral protein 1. Cryo-electron microscopy revealed that these changes affect the assembly of intermediate viral states (particle A and E), suggesting that the mechanism for reduced heat sensitivity could be related to improved molecular packing of CVB5, resulting in greater stability and/or altered dynamics of virus uncoating during infection.

microbiology↗

bioRxiv2023

A HEV ORF2 protein-mediated mechanism of hepatitis E associated kidney disease.

Hepatitis E virus (HEV) infection, one of the most common forms of hepatitis worldwide, is often associated with extrahepatic, particularly renal, manifestations. However, the underlying mechanisms are incompletely understood. Here, we report the development of a de novo immune complex-mediated glomerulonephritis (GN) in a kidney transplant recipient with chronic hepatitis E. Applying immunostaining, electron microscopy, and mass spectrometry after laser-capture microdissection, we show that GN developed in parallel with increasing glomerular deposition of a noninfectious form of HEV open reading frame 2 (ORF2, capsid) protein secreted in excess. HEV particles or RNA, however, were not detectable. Patients with acute hepatitis E displayed similar but less pronounced deposits. Our results elucidate an immunologic mechanism by which this hepatotropic virus causes variable renal manifestations and establish a link between the HEV ORF2 protein and hepatitis E-associated GN. They directly provide a tool for etiology-based diagnosis of HEV-associated GN as a distinct entity and suggest therapeutic implications.

pathology↗